im doing cleaning validation, but i confused bout acceptance criteria for cleaning validation.

the requirement for acceptance criteria in my country is 10 ppm (MAC).

now, if i doing cleaning validation for liquid filling for product A, then what ppm the acceptance criteria for the next product (product B). the batch size for product B is 300L. and I took the rinse water for cleaning validation 3L.

thank you

First of all let me understand you work. The MAC or MAR is the allowable residue of product A (previous product) in product B & the value comes in unit of mass i.e. mg or micro gm, etc. The mathematical expression is:

MAC=(TD X BS X SF)/LDD where TD= smallest therapeutic dose of product A

BS= Batch size of product B

SF= Safety factor (0.001)

LDD= largest daily dose of product B

Now, after calculating the MAC, it is time to express this value in equipment surface contamination because the ultimate objective is to evaluate cleanliness of the manufacturing equipments.

Surface contamination= MAC/ Shared Equipment Surface Area of entire train (in sq. cm or sq. inch). The value will come in mg/sq.cm or micro gm/sq. inch or like wise.

If you want to carry out rinse sampling, consider the single rinse volume say 5 ltr. exposing entire equipment surface.

The expression will be= mg/sq. cm X surface area of that equipment/ 5 lts.

It is now easy to convert the out come of above formula in ppm bcoz mg/lt. is ppm.

Hope I am able make some sense, isn’t it. Waiting your views.

Mr. Shambhu, the formula you have provided is based on the dose criterion whereas rika ndry is asking for 10 ppm criterion.

The general practice should be determine both the 10 ppm and 0.1% dose criterion and select the most stringent limit among the twos.

For calculating limit for 10 ppm,

MAR = 10 ppm x BSs

Where, MAR is Maximum Allowable Residue & BSs is Batch size of Subsequent Product. As a worst case scenario you can chose the minimum batch size among all the products that are manufactured under that particular equipment/facilities.

Dear Rika ndry,

As per the informations you have provided, your BSs is 300 L, so the MAR i.e. your limit will be 10 ppm X 300 L = 3 ml.

Hope this will help you,

Prawan Dahal

thank for the reply. for Mr Shambu and Mr Prawan.

but i want to know the mathematical expression for Surface contamination= MAC/ Shared Equipment Surface Area of entire train (in sq. cm or sq. inch). used for what method the rinse or swab test?

and if i used the mathematical expression :MAC=(TD X BS X SF)/LDD where TD= smallest therapeutic dose of product A

BS= Batch size of product B

SF= Safety factor (0.001)

LDD= largest daily dose of product B

the result would be in L, right?

and if i used Mr Shambu method, the limit will be 3gram.not 3 ml.

thank before

thank for the reply.

and if i used your method, the limit will be 3gram.not 3 ml.

thank you

First of this therapeutic approach of determining acceptance criteria is all about considering API as the primary source of contamination and practically it is dispensed & calculated in unit of mass (kg, mg, micro gm, etc.). Where as Ltr. or ml or micro ltr. are the units of volume.

Thats why the label claim is always expressed as mg/ml, or micro gm/ml. in liquid formulation, isn’t it ?

Let me site one example to make it bit clear for you.

Assume that product A has an active at a level of 2000 micro gm/mL and is dosed at 5 mL from three to five times daily.

The minimum daily dose would be

(2000 micro gm/mL) X (5 mL/dose) X (3 doses/day) = 30,000 micro gm/day

If one also assumes that product B is dosed at 5 mL from two to four times a day, then the maximum daily dose of product B would be

5 mL/dose X 4 doses/day = 20 mL/day

Rika ndry & daprawan your comments are highly expected.

i have found the mathematical expression for cleaning validation using 10 ppm criterion.

now, if i doing cleaning validation for liquid filling for product A, the batch size for product B is 300L. and I took the rinse water for cleaning validation 500mL.

the mathematical expression will be :

the concetration of active ingredient in Product A(after determine using HPLC/etc) per mL, in e.q 9 ppm(mg/L).

then we multiplies with rinse water that we take (500mL/0,5L).

9mg/L x 0,5 L = 4,5 mg.

after that we use mathematical expression :

MAC = 4,5 mg x 1.000.000 ppm/300.000.000 mg

= 0,015 ppm.(MAC for the active ingredient in the next batch)

300L (consider the specific gravity is 1,0 g/mL).= 300 Kg = 300.000.000mg

Lets finish the discussion on units to be selected. Whatever the unit you select it should be considered the content per ml. Both the units are interchangeable via weight per ml. If your product have 5 mg per ml, then 3 ml will be equivalent to 15 mg and 15 mg will be equivalent to 3 ml. So, do not get confusions with the units.